TTA / TetOff Atlas II (PrP/CamKII)

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About

The tetracycline-responsive (TetR) gene system is a binary transgenic system in which transgene expression may be activated or silenced by administration of tetracycline, or its derivates (Gossen and Bujard, PNAS 89:5547-5551, 1992; Gossen et al., Science 286:1766-1769, 1995). Such animal models are generated by crossing two different mouse lines, one with a gene modulator (promoter mouse line) and one with the actual disease-causing gene (responder mouse line). In the double transgenic offspring both the regional distribution and intensity of target gene expression depend on the activity of the chosen promoter controlling the expression of a gene activator, which in turn is accessible for experimental modulation. Detailed knowledge about where in the brain gene expression is regulated is essential for the use and interpretation of such models.

The TetOff atlas 2 (PrP/CamKII) is an interactive resource providing access to a collection of microscopic brain sections displaying the spatial distribution patterns of promoter activity of two popular transgenic tetracycline-responsive (Tet-Off) promoter mouse lines, the prion protein (PrP) mouse line (previously reported in Boy et al., Neuroimage 33:449-462, 2006) and the Ca2+/calmodulin-dependent protein kinase II (CamKII).  

Access image repository

The virtual microscopy viewer allows interactive zooming and panning. Original images are available for download via separate link. Each section has been annotated with names of key landmarks, regions, nuclei, and areas.

Re-use of data from this repository is allowed provided that reference is given to the following publications: 

  • CamKII: Odeh F, Leergaard TB, Boy J, Schmidt T, Riess O, Bjaalie JG. Atlas of transgenic Tet-Off Ca2+/calmodulin-dependent protein kinase II and prion protein promoter activity in the mouse brain. NeuroImage 54:2603-2611, 2011 
  • PrP: Boy J, Leergaard TB, Schmidt T, Odeh F, Bichelmeier U, Nuber S, Holzmann C, Wree A, Prusiner SB, Bujard HB, Riess O, Bjaalie JG. Expression mapping of tetracycline-responsive prion protein promoter: digital atlasing for generating cell-specific disease-models. NeuroImage 33:449-462, 2006 
Animal # Genotype Image repository Download original
388.17 Prnp-tTA:βGal Filmstrip viewer Tiffs
317.8 CamKII-tTA:βGal Filmstrip viewer Tiffs

Experimental procedures in brief

The atlas is based on data from two double transgenic mice, a 40 week old female CamKII/LacZ mouse and a 5 week old female PrP/LacZ mouse (Boy et al., NeuroImage 33: 449-462, 2006). For methodological details concerning gene construct, preparation of histological material, image acquisition, and atlas construction, see Boy et al. (NeuroImage, 33:449-462, 2006), and Odeh et al. (NeuroImage 54:2603-2611, 2011).

In brief, double-transgenic mice were generated by cross-breeding a CamKII or PrP promoter mouse line with a LacZ responder mouse line. Animals were anaesthetized and transcardially perfused with 4% paraformaledhyde before brains were removed and stained using X-Gal (to label the LacZ product β-galactosidase) and counterstained with Cresyl violet (sections from the CamKII/LacZ brain) or Neutral red (sections from the PrP/LacZ brain). High resolution section images were obtained using an automated Olympus Bx52 microscope equipped with a high-precision motorized stage running the Neurolucida v6.0 Virtual Slice software (MicroBrightField Inc., Williston, VT, USA).

The X-gal staining gives an intense dark-blue labeling at sites with presence of β-galactosidase, which is encoded by the LacZ reporter gene, controlled by the Tet-Off promoters. Presence of labeling thus indicates CamKII or PrP activity, respectively.  

All coordinates, annotations and abbreviations used to label and facilitate section identification, are in accordance with the mouse brain atlas by Paxinos and Franklin: The Mouse Brain in Stereotaxic Coordinates, Academic Press, 2001.

History

  • 2010-11 TetOff atlas II(PrP/CamKII) released in conjunction with original report by Odeh et al., NeuroImage 54:2603-2611, 2011
  • 2009-09 Poster / demonstration of comparative CamKII and PrP promoter activity distributions. 2nd INCF Congress of Neuroinformatics, Plzen, Czeck Republic
  • 2006-05 TetOff atlas I(PrP) released. First online digital atlas of the distribution of tetracycline-response protein promoter expression at cellular resolution throughout the mouse brain. Reported in Boy et al., NeuroImage 33: 449-462, 2006

Contributing laboratories

  • Department of Medical Genetics, University of Tübingen, Calwerstrasse 7, D-72076 Tübingen, Germany. People: Jana Boy, Thorsten Schmidt, Ulrike Bichelmeier, Silke Nuber, Olaf Riess
  • Neural Systems Laboratory (http://www.nesys.uio.no), Centre for Molecular Biology and Neuroscience & Institute of Basic Medical Sciences, Department of Anatomy, University of Oslo, P.O. Box 1105 Blindern, N - 0317 Oslo, Norway: Histological processing, image acquisition, development of atlas repository. People: Francis Odeh, Jan O. Kjøde, Ivar A. Moene, Trygve B. Leergaard, Jan G. Bjaalie

Funded by

  • Fritz Thyssen Stiftung
  • The Deutsche Heredo-Ataxie-Gesellschaft
  • The European Union (6th Framework Programme, EUROSCA)
  • The European Union (QLG3-CT-2001-02256)
  • The Research Council of Norway
  • The neuroinformatics components of this resource were funded by the Human Brain Project through the European Union Seventh Framework Program (FP7/2007-2013) under grant agreement no. 604102 (HBP)

Contact

j.g.bjaalie@medisin.uio.no